Methods of treating a cardiac arrhythmia by thoracoscopic production of a Cox maze III lesion set

ABSTRACT

Methods of treating a subject for a cardiac arrhythmia are provided. Aspects of the methods include thoracoscopically producing a cardiac Cox maze III set of lesions in cardiac tissue of the subject in a manner sufficient to treat the subject for the cardiac arrhythmia.

Pursuant to 35 U.S.C. §119 (e), this application claims priority to thefiling date of the U.S. Provisional Patent Application Ser. No.60/023,811 filed Jan. 25, 2008; the disclosure of which application isherein incorporated by reference.

INTRODUCTION

Atrial fibrillation (AF) is the most common form of cardiac arrhythmialeading to hospital admission. Over 2.2 million Americans are affectedby AF and approximately 160,000 new cases are identified annually. Inaddition, the risk for atrial fibrillation increases with aging. It isestimated that subjects over 80 years of age have a 10% chance of havingatrial fibrillation. The ideal of treating large numbers of patientswith isolated AF has remained elusive due to the invasiveness of the Coxmaze III operation, which is considered to be the gold standard forsurgical therapy of atrial fibrillation.

The past several years have seen the development of a number ofprocedures that have attempted to treat AF with a less invasiveapproach. Ablative therapies for AF, including both catheter andsurgical therapies, have undergone a significant change by devisinglesion sets modeled after the Maze operation. Nonicisional ablativemodalities have also proliferated and include cryoablation, microwave,radiofrequency, laser, and high-intensity focused ultrasound. However,none of these approaches are able to provide a complete Cox maze III setof lesions through a thoracoscopic approach.

SUMMARY

Methods of treating a subject for a cardiac arrhythmia are provided.Aspects of the methods include thoracoscopically producing a cardiac Coxmaze III set of lesions in cardiac tissue of the subject in a mannersufficient to treat the subject for the cardiac arrhythmia.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 provides a schematic view of the chest, demonstrating anembodiment of the access ports used to perform the methods of theinvention.

FIG. 2 provides a schematic view of the heart, demonstrating thethoracoscopic access to the epicardial region of the heart according tothe methods of the invention.

FIG. 3 provides a schematic view of the heart, demonstrating anembodiment of the clamping method which can be used according to methodsof the invention.

FIG. 4 provides a schematic view of the heart, demonstrating a map ofthe ablation lesions that can be created using the methods of thesubject invention.

DETAILED DESCRIPTION

Methods of treating a subject for a cardiac arrhythmia are provided.Aspects of the methods include thoracoscopically producing a cardiac Coxmaze III set of lesions in cardiac tissue of the subject in a mannersufficient to treat the subject for the cardiac arrhythmia.

Before the present invention is described in greater detail, it is to beunderstood that this invention is not limited to particular embodimentsdescribed, as such may, of course, vary. It is also to be understoodthat the terminology used herein is for the purpose of describingparticular embodiments only, and is not intended to be limiting, sincethe scope of the present invention will be limited only by the appendedclaims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges and are also encompassed within the invention, subject toany specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either orboth of those included limits are also included in the invention.

Certain ranges are presented herein with numerical values being precededby the term “about.” The term “about” is used herein to provide literalsupport for the exact number that it precedes, as well as a number thatis near to or approximately the number that the term precedes. Indetermining whether a number is near to or approximately a specificallyrecited number, the near or approximating unrecited number may be anumber which, in the context in which it is presented, provides thesubstantial equivalent of the specifically recited number.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present invention, representativeillustrative methods and materials are now described.

All publications and patents cited in this specification are hereinincorporated by reference as if each individual publication or patentwere specifically and individually indicated to be incorporated byreference and are incorporated herein by reference to disclose anddescribe the methods and/or materials in connection with which thepublications are cited. The citation of any publication is for itsdisclosure prior to the filing date and should not be construed as anadmission that the present invention is not entitled to antedate suchpublication by virtue of prior invention. Further, the dates ofpublication provided may be different from the actual publication dateswhich may need to be independently confirmed.

It is noted that, as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. It is further noted that the claimsmay be drafted to exclude any optional element. As such, this statementis intended to serve as antecedent basis for use of such exclusiveterminology as “solely,” “only” and the like in connection with therecitation of claim elements, or use of a “negative” limitation.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentinvention. Any recited method can be carried out in the order of eventsrecited or in any other order which is logically possible.

Methods

As summarized above, aspects of the methods include thoracoscopicallyproducing a Cox maze III set of lesions in a subject. By“thoracoscopically producing” or “thoracoscopically” is meant methodswhich are performed through one or more thoracoscopic body openingsusing a thoracoscope or a thoracoscopic instrument for procedures suchas visualization, surgery, the conduction of diagnostic tests, etc., inor adjacent to the thoracic cavity. Similarly, a “thoracoscopicprocedure” is a procedure in which visualization, surgery, a diagnostictest, etc., is performed by gaining access to the chest through one ormore thoracoscopic body openings using a thoracoscope, or athoracoscopic instrument.

By “thoracoscope” or “thoracoscopic instrument” is meant a thintube-like instrument used to examine or enter the inside of the thoraciccavity of a subject, e.g., the pleural space of a subject. Athoracoscope is a type of endoscope, which is a general term for a thintube-like instrument for examining the inside of the body. Athoracoscope can have a light and a lens or camera for viewing theinside of the chest, and can also have one or more tools that can beused with a thoracoscope, such as a sewing device, a cutting device, anablation device, a grasping device, a retracting device, etc. In someembodiments, a single thoracoscopic instrument can have more than onefunction (e.g., camera and cutting functions, or light and sewingfunctions, etc.) In addition, although the methods discussed belowdisclose the use of a particular number of thoracoscopic instruments,the methods of the invention can include using any suitable number ofthoracoscopic instruments, such as one or more, two or more, three ormore, four or more, etc. In addition, the methods can include use of thethoracoscopic instruments sequentially, or simultaneously, includingsimultaneous use of bilateral thoracoscopic instruments.

Access to the thoracic cavity can be achieved by percutaneously creatinga opening into the chest cavity through a skin incision in theintercostal space (ICS) between two adjacent ribs, and inserting aninstrument such as a trocar, cannula, thoracoscope, thoracoscopicinstrument or the like through the opening. One or more openings, or“ports” can be created in one or more locations in the intercostalspaces of the chest, depending on the procedure to be performed and thethoracoscopic instruments to be used. One or more thoracoscopes orthoracoscopic instruments can be advanced through at least one of theopenings, or thoracoscopic body openings. The creation of additionalopenings can allow for the use of accessory instruments. In someembodiments, a pneumothorax is created during the thoracoscopicprocedure, i.e., CO₂ is introduced into the pleural space whichsurrounds the lung, to collapse the lung and improve the view of thesurgical field.

The methods of the subject invention are minimally-invasive methods,such that the thoracoscopic body openings created in the subject's bodyare small, for example, 3 centimeters or less in greatest dimension, 2centimeters or less in greatest dimension, 12 millimeters or less ingreatest dimension, or 5 millimeters or less in greatest dimension. Insome embodiments, all of the thoracoscopic body openings created in thesubject's body measure no more than 12 millimeters in greatestdimension. In some embodiments, therefore, “thoracoscopically producing”includes making a thoracoscopic body opening that measures no more than12 mm in greatest dimension. In some embodiments, “thoracoscopicallyproducing” includes making all of the thoracoscopic body openings nomore than 12 millimeters in greatest dimension. This is in contrast to a“mini-thoracotomy” in which an incision which can measure 5 centimetersor 8 centimeters or more is utilized for gaining access to the thoraciccavity. The thoracoscopic methods can allow access to the epicardialsurface of the heart.

In some embodiments, the thoracoscopic body openings or ports areproduced bilaterally, i.e., on both sides of the subject's body. In someembodiments, the number of thoracoscopic body openings or ports mayrange from 2 to 6 ports on each side, such as from 3 to 5 ports, or 4ports on each side. The number of ports produced can vary depending onthe subject, the procedure to be performed, the lesions to be created,and the thoracoscopic instruments to be used.

In one embodiment, the thoracoscopic body openings that are created onthe right side of a subject include an opening in the 2^(nd) or 3^(rd)ICS, 1 to 2 centimeters medial to the anterior axillary line; an openingin the 4^(th) ICS 1 to 2 centimeters posterior to the anterior axillaryline; an opening in the 5^(th) ICS in the mid-axillary line; and anopening in the 6^(th) ICS in the anterior axillary line. In someembodiments, the thoracoscopic body openings that are created on theleft side of a subject include an opening in the 2^(nd) ICS 1 to 2 cmmedial to anterior axillary line; an opening in the 3^(rd) or 4^(th) ICS1 to 2 centimeters posterior to the anterior axillary line; an openingin the 5^(th) ICS in the mid-axillary line; and an opening in the 6^(th)ICS in the anterior axillary line. In some embodiments, at least one ofthe thoracoscopic body openings is an opening in the 2^(nd) ICS oneither the right or left side. In other embodiments, at least one of thethoracoscopic body openings is an opening in the 3^(rd) ICS, locatedmedial, or anterior to the anterior axillary line on either the right orleft side. Although the above combination of ICS openings can be used insome embodiments of the invention, the methods can include placement ofthoracoscopic body openings which can vary in location, for example, anopening in the 6^(th) ICS can be 1 centimeter posterior to the anterioraxillary line, or more than one opening can be made in the same ICS.

As discussed above, the Cox maze III procedure is a type of heartsurgery for treatment of atrial fibrillation. The surgery as describedis done via a median sternotomy (vertical incision through thebreastbone), and cardiopulmonary bypass (stopping the heart andcirculating the blood outside of the body) in order to create a “maze”,or an extensive series of incisions that are made in the wall of theatria in a maze-like pattern. The incisions which are subsequentlysutured back together result in areas of scar in the cardiac tissuewhich can block the abnormal electrical circuits that are seen in AF.The goal of the procedure is therefore to eliminate atrial fibrillationand have the patient return to a normal sinus rhythm as a result of thescarring in the region of the incisions.

In the methods of the subject invention, a Cox maze III set of lesionsis be thoracoscopically produced, i.e., without the need for a mediansternotomy, or even a mini-thoracotomy (e.g., a chest incision of 5centimeters). In methods of the invention, a “lesion” or “scar” can becreated by ablating cardiac tissue from the epicardial surface of theheart, which is in contrast to methods of creating the lesions from theendocardial surface, or inside surface, of the heart as with an opensurgery or a catheter procedure. By “lesion” or “ablation line” is meantan area of cardiac tissue that has been ablated. By “ablation” is meanta process of removing or altering the electrically-conducting tissue inan area of interest, such that the tissue no longer conducts orgenerates an electrical impulse sufficient to generate or propagate anarrhythmia. The process of ablation can prevent an arrhythmia fromdeveloping because the cardiac tissue which provides a trigger for anarrhythmia has been destroyed. The process of ablation can also preventan arrhythmia from propagating to other areas of the heart by thecreation of a line, or lesion, which electrically isolates the tissueand blocks passage of the electrical impulse. Ablation can be performedwith a variety of types of energy, such as radiofrequency energy, laserenergy, microwave energy, cryothermy, and the like. Ablation “lines” or“lesions” can be focal areas which are separate from other areas ofablation, or they can be contiguous, such they form lines or lesionsconnected to each other, which can form, for example, a continuous line,or ring, or circle, in order to electrically isolate an area of cardiactissue.

By “Cox maze III” set of lesions is meant a group of lesions chosen fromamong the following ablation lines: a right pulmonary vein encirclingablation line 410 as shown in FIG. 4, a left pulmonary vein encirclingablation line 420, a superior connecting ablation line connecting theright and left pulmonary vein encircling lines 430, an inferiorconnecting ablation line connecting the right and left pulmonary veinencircling lines 440, an ablation line connecting the superior ablationline to the fibrous trigone 450, an ablation line connecting thesuperior ablation line to the base of the left atrial appendage 460, andan ablation line extending from the inferior connecting ablation line tothe coronary sinus 480. The combination of ablation lines 410, 420, 430,and 440 comprises what is known as the “box lesion” set. As such, insome instances, the Cox maze III lesion set produced by methods of theinvention is a box lesion set.

In some embodiments, the set of lesions making up the Cox Maze IIIlesion set according to the methods of the subject invention furtherincludes one or more additional lesions in addition to the box lesionset. In some instances, Cox Maze III lesion sets of the invention mayinclude amputation of the left atrial appendage, or a left atrialappendectomy (element 470). In some embodiments, the set of lesionsproduced by methods of the invention further includes an ablation linein the posterolateral wall of the right atrium connecting the superiorvena cava to the inferior vena cava, shown as element 500 in FIG. 4. Insome embodiments, the set of lesions also includes an ablation lineconnecting the right pulmonary vein encircling ablation line to anablation line in the posterolateral wall of the right atrium connectingthe superior vena cava to the inferior vena cava, shown as element 490in FIG. 4. In some embodiments, the methods of the subject inventionfurther include ablation of autonomic ganglionic plexi on the epicardialsurface of the atrium. In some embodiments, the methods of the subjectinvention can include ablation of complex fractionated atrialelectrograms, discussed further below.

In some instances, the methods include first identifying a subject inneed of surgical treatment for a cardiac arrhythmia. A subject who needssurgical treatment for an arrhythmia can include, for example, subjectswho are symptomatic, subjects who are asymptomatic but cannot beadequately anticoagulated to reduce their risk of stroke, subjects whohave failed medical therapy, subjects who have failed catheter ablation,subjects who cannot tolerate the side effects of anti-arrhythmic drugs,or subjects who choose surgical ablation as a preferred method.

A patient in need of surgical treatment for a cardiac arrhythmia can beprepared for surgery in the conventional manner. General anesthesia,when desired, can be provided using any convenient protocol, e.g., viaadministration of an anesthetic agent with a double-lumen endotrachealtube in order to provide single lung ventilation. In some embodiments,transesophageal echocardiography monitoring is performed during theentire procedure.

The methods of the subject invention can be performed on a beatingheart, i.e., without cardiopulmonary bypass, and the methods can also beperformed in a patient on cardiopulmonary bypass, i.e., a stopped heart.The procedure may be performed on the right side first, followed by theleft side as outlined below, or alternatively, the procedure may beperformed on the left side first, followed by the right side.

For a right thoracoscopic approach, the operating table can be tiltedslightly to the left side with a slight tilt, such as a 15 degree tilt.After the right lung is deflated, one or more ports, or openings, can becreated in the right side of the chest, as disclosed above. In oneembodiment, as shown in FIG. 1, four ports can be utilized forperforming the methods of the subject invention. In FIG. 1, a first portis placed in the 4^(th) intercostal space (ICS) 1 centimeter posteriorto the anterior axillary line, shown as element 110. A thoracoscope canthen be introduced and the right hemithorax visually inspected.Humidified CO₂ can be introduced into the thoracic cavity at a pressuresufficient to allow adequate visualization for the methods of theinvention (e.g., 8 mm Hg pressure). This pressure can be maintainedthroughout the procedure. A second port can be placed in the 2^(nd) or3^(rd) ICS 1 to 2 cm medial to anterior axillary line, shown as element120 in FIG. 1. The placement of this most cephalad port, in the 2^(nd)or 3^(rd) ICS 1 to 2 cm medial to anterior axillary line, allows for thecreation of a lesion in the region of the aorto-mitral confluence, oranterior fibrous trigone. A third port can be placed in the 5^(th) ICSmid-axillary line, shown as element 130 in FIG. 1. A fourth port,element 140 in FIG. 1, can be placed in the 6^(th) ICS in the anterioraxillary line.

A second grasping forceps can then be introduced through any of thethree other ports. A first opening is created in the pericardium, whichis the fibrous sac surrounding the heart, to allow access to theepicardial surface of the heart. In some embodiments, the pericardium isopened cephalad to, or just above, the confluence of the right atrialappendage and ascending aorta. The pericardial opening can be locatedapproximately 1 to 2 cm anterior and parallel to the right phrenicnerve. This opening can be extended cephalad, or in a superiordirection, e.g., to the level of the aorta, and can then be extendedinferiorly, e.g., to the level of the inferior vena cava (IVC), or tothe level of the diaphragm.

One or more traction sutures can be placed in the pericardial tissue, inorder to retract the edges of the pericardium away from the pulmonaryveins. These traction sutures can be placed utilizing an Endo Stitch™(Autosuture™, Covidien, Mansfield, Mass.), for example, or other similarsuture device designed to be used with a thoracoscope. The ends of theone or more traction sutures are exteriorized, or brought outside one ofthe port incisions, and secured.

Both the oblique sinus (element 201 in FIG. 2) and transverse sinus(element 202 in FIG. 2) can then be opened using both sharp and bluntdissection techniques. The oblique sinus can be opened bluntly by usingone or more endoscopic soft tissue dissectors (for example, using anendoscopic Kittner, which is a Dacron™ coated soft tip tissue dissector,or any other soft tissue dissector suitable for use with an endoscopicor thoracoscopic instrument). The oblique sinus is one of twopericardial sinuses (oblique and transverse) which are pouches orcul-de-sacs of the pericardium located behind the heart. The obliquesinus is located behind the left atrium, between the right and leftpulmonary veins. The right thoracoscopic approach to the oblique sinusis shown as element 250 in FIG. 2, which is a schematic view of theposterior wall of heart as viewed from the front, with the remainder ofthe heart removed for clarity. Additional anatomic landmarks shown inFIG. 2 include the superior 205 and inferior 206 venae cavae, ascendingaorta 207, pulmonary artery 208, and diaphragm 209.

The transverse sinus 202 can then be entered by retracting the SVCanteriorly, and entering between the superior vena cava above and thepulmonary veins below. The retraction of the SVC can be facilitated byusing a soft tissue dissector as described above, which has beeninserted through one of the superior ports, e.g., a port in the 2^(nd)or 3^(rd) ICS. Entry into the transverse sinus is confirmed withvisualization of the left atrial appendage. The right thoracoscopicapproach to the transverse sinus is shown as element 260 in FIG. 2. Anarticulating or hinged dissector with a firm tip, such as the Wolf™Lumitip™ dissector (Atricure, Inc., Cincinnati, Ohio) can be introducedthrough the oblique sinus and then maneuvered behind the heart until thetip exits the transverse sinus posterior to the right set of pulmonaryveins. Any other suitable dissector may be used with the subject methodssuch as a curved Satinsky clamp, for example. In some embodiments, thedissector can have a light on the tip of the dissector. After thedissector reaches the transverse sinus, the posterior space between thepericardium and left atrium can be enlarged with blunt dissection. Thedissector is then removed.

In some embodiments, a combination ablation and sensing device such asthe Isolator® Multifunctional Pen (Atricure, Inc., Cincinnati, Ohio) canbe introduced into the thoracic cavity via any of the three ports. Thesensing portion of the device can be used to sense the pulmonary veins,to create a baseline map of the right pulmonary vein potentials.Additionally, in some embodiments, the methods can also include sensingin order to localize the ganglionic plexi. Autonomic ganglionic plexi(GP) are collections of nerves located on the surface of the heart.Autonomic GP can promote pulmonary vein arrhythmogenicity and facilitateinduction of sustained atrial fibrillation by premature atrialdepolarizations. The autonomic GP can therefore function as regulatorsof both pulmonary vein- and non-pulmonary vein-dependent mechanisms ofatrial fibrillation. The GP can be mapped with high-frequencystimulation (e.g., at a rate of 800-1,000 impulses per minute), at avoltage (e.g., 18 volts) using any suitable sensing device. When the GPare stimulated they release acetylcholine, a neurotransmitter which is apotent blocker of the atrioventricular node (AV) node, the area ofspecialized tissue between the atria and the ventricles of the heartwhich conducts the normal electrical impulse from the atria to theventricles. Acetylcholine can also slow down the sinoatrial node (SAnode or sinus node) as well, which is the impulse-generating (pacemaker)tissue located in the right atrium of the heart, and thus the generatorof sinus rhythm.

Release of acetylcholine by a stimulated GP can result in a significantdecrease in heart rate (a bradycardic response). If a significantbradycardic response is seen (e.g., an increase in R-R of 50% orgreater) after stimulation of a GP, this confirms the presence of anactive GP which can be focally ablated. If there is no response when anarea of tissue is stimulated (e.g., no significant increase in the R-Rinterval during stimulation) the stimulating device can be moved, andanother area can be tested.

In some instances, a stimulating device, such as the pen disclosedabove, can be placed in a location where a ganglionic plexus is known tobe located, and then the ablating agent can be activated (e.g.,radiofrequency energy), and the ganglionic plexus can be focallyablated. One or more ganglionic plexi can be ablated from the epicardialapproach, using the devices as disclosed above. The methods can includerepeating the ablating steps if necessary one or more times until it isdetermined that the GP has been ablated (e.g. no significant increase inthe R-R interval is seen during stimulation). Further details oftechniques of GP mapping and ablation that can be adapted for use withthe subject methods are disclosed, for example, in the publication byMehall, et al., entitled “Intraoperative Epicardial ElectrophysiologicMapping and Isolation of Autonomic Ganglionic Plexi”. Therefore, in someembodiments, the methods can include thoracoscopically producing alesion in a ganglionic plexus. After this step, the above sensing stepscan be repeated to confirm conduction block post-ablation, discussedfurther below. The evaluation of ablation can be performed with theIsolator® Multifunctional Pen, or any other device suitable forthoracoscopic procedures that performs a similar function. Thestimulating and sensing device can then be removed.

As discussed above, by “ablation” is meant a process of removing oraltering the electrically-conducting tissue in an area of interest(e.g., a GP) such that the tissue no longer conducts or generates anelectrical impulse sufficient to generate or propagate an arrhythmia. Insome embodiments, ablation can be performed by directly contacting aportion of cardiac tissue with an ablation device, in a mannersufficient to create a lesion. In other embodiments, ablation can beperformed by delivery of an ablating agent to cardiac tissue. Forexample, in some embodiments, an ablation device can be locatedsufficiently close to an area of cardiac tissue of interest, such thatan ablating agent, (e.g., laser energy) is delivered to the cardiactissue in a manner sufficient to create a lesion. The form of energyused for ablating cardiac tissue can be radiofrequency or cryoablationenergy, for example. In some embodiments the ablation is transmural,i.e., extends through the entire heart wall. In other embodiments, theablation does not extend through the entire thickness of the cardiacwall; however, the degree of ablation may be sufficient to blockelectrical conduction. Any suitable device can be used for ablation,such as the Isolator® Multifunctional Pen disclosed above, or othersimilar device such as the Cardioblate™ Ablation System (Medtronic,Minneapolis, Minn.), the AFx FLEX 10™ microwave ablation probe (Guidantcorporation), the Surgifrost™ Cryoablation System (CryocathTechnologies), or the Epicor™ High Intensity Focused Ultrasound CardiacAblation system (St Jude Medical, St Paul, Minn.), for example.

The methods of ablation can include contacting a portion of cardiactissue with an ablation device to form a lesion. The methods can furtherinclude repeating the contacting and ablating steps a number of times toproduce a plurality of lesions. For example, the contacting step may beperformed two or more times, such as three or more, or four or moretimes, etc. In some embodiments, the contacting and ablating step isperformed in the same location. In some embodiments, the contacting andablating step can be performed in overlapping locations, such that partof a second location overlaps with part of a first ablating location,such as in the case of creating a continuous linear ablation line. Inother embodiments, a second ablation step may be in a different locationfrom the first ablation step, as in the ablation of a ganglionic plexusor a complex fractionated atrial electrogram, discussed further below.Although the methods of ablation as described use contact of cardiactissue in order to achieve ablation, in some embodiments ablation can beachieved by using an ablation device in proximity to cardiac tissue, forexample, in delivering an ablation agent to the cardiac tissue.

The devices that can be used with embodiments of the invention aredevices that are configured to ablate, or remove, or sufficiently alterelectrically-conducting cardiac tissue. In some embodiments, theablation is achieved by using a form of energy, such as radiofrequencyor cryoablation energy. The subject devices are devices that can be usedin endovascular, minimally invasive surgical, open surgical, or otherinterventional procedures. Any suitable device can be used for ablation,such as the ablation devices disclosed above, or other similar devicessuch as those devices in the Cardioblate™ Ablation System (Medtronic,Minneapolis, Minn.), the AFx FLEX 10™ microwave ablation probe (Guidantcorporation), the SurgiFrost®/FrostByte™ Cryoablation System (CryocathTechnologies), or the Epicor™ High Intensity Focused Ultrasound CardiacAblation system (St Jude Medical, St Paul, Minn.), for example.

An ablation device of the subject methods can be in the shape of aclamp, with an upper and a lower jaw, such that the ablation device is aclamping device. In other embodiments, the ablation device can have anelongated cylindrical shape, such as that of a pen. In some embodiments,the ablation device can have a linear shape, a rectangular shape, asemi-circular shape, an “L” shape, a “U” shape, or any other suitableshape. The configuration of the surface of the ablation device thatcontacts the tissue can also be any suitable two-dimensional shape suchas a line, a square, an oval, a triangle, etc. In some embodiments, theablation device can further employ suction to pull tissue into thedevice.

The area of cardiac tissue that is ablated will depend on the type ofablation device (e.g., clamp, or pen) and the shape of the portion ofthe ablation device that contacts the tissue (e.g., rectangular area;circular area). The total area of cardiac tissue that is ablated willfurther depend on the type and strength of the energy used (e.g.,radiofrequency (RF) energy, high intensity focused ultrasound energy)and the length of time that the device is in contact with tissue, forexample.

For example, an elongated cylindrical device may have a circular area atone end of the device that of contacts cardiac tissue, and afterapplication of the ablating energy may form an area of ablated tissuethat approximates a cone-shaped area of tissue, extending to aparticular depth, such as 6 mm, for example. In the case of an ablationdevice in the shape of a clamp, the area of the ablated tissue betweenthe jaws of the clamp can be a rectangular area, with the approximatedimensions of the clamp. For example, if the jaws of the clamp are each4 cm long and 5 mm wide, the ablated area can be a rectangular area 4 cmin length and 5 mm in width, with a depth equal to the area of tissuebetween the jaws of the clamp. In some embodiments, the area of ablatedtissue may be greater than the area which was in direct contact with theablation device, such as 10% greater or more, or 20% greater or more,etc. Furthermore, the shape of the ablated area once ablation has beencompleted can be any suitable three-dimensional shape such as acylinder, cone, pyramid, cube, sphere, etc.

The ablation device can include, but is not limited to devices that useradiofrequency (RF) energy, including bipolar radiofrequency energy orbipolar irrigated RF energy, cryoablation, laser energy, microwaveenergy, thermal energy, a thermoelectric chip device, ultrasound energy,including high intensity focused ultrasound energy, an ablating drugdelivery device, and any combinations thereof. For example, the ablationdevice can be a bipolar radiofrequency (RF) device such as the Isolator®Synergy™ Cardiac Ablation Clamp (Atricure, Inc., Cincinnati, Ohio). Thissystem consists of a power generator, bipolar clamp, and a pacing,sensing, stimulator, bipolar RF pen. The device delivers RF energy withresultant heating of the tissue and can complete a transmural lesion.The term bipolar indicates that the ablation path extends locallybetween two electrodes in the device, rather than between one electrodeand a general remote, or external electrode. Although the currentmethods can be used with this system, the technique is equallyapplicable to other types of ablation devices. For example, in someembodiments, the ablation device can be a laser energy device, amicrowave energy device, a thermal energy device, an ultrasound device,a cryoablation device, etc. In some embodiments, the methods can includeother methods of ablation, such as surgical incision.

The process of ablation can be performed by direct contact of theablation device with cardiac tissue, and in some embodiments ablationcan be performed with delivery of an ablation agent in sufficientproximity to the cardiac tissue of interest. The process of ablation iscontinued until sufficient conduction block is achieved in the desiredarea. This can require 1 to 4 or more applications of the device oragent, such as two applications or more, or three applications or more,etc. In addition, the process of ablation can be monitored as theablation is performed. In some embodiments, the process of ablation canbe guided by a feedback parameter, such as impedance, temperature,conductivity, etc. For example, if radiofrequency energy is used, theimpedance of the tissue can be monitored and the power output of thedevice can be designed so that it is inversely proportional to theimpedance of the tissue, such that overheating of the tissue does notoccur. In some embodiments, the process of ablation can be continued fora specific period of time, which can be determined by the thickness orcomposition of the tissue to be ablated, or the anatomical location ofthe tissue to be ablated, for example.

The subject methods may also include intraoperative electrophysiologictesting of the cardiac tissue to confirm the presence of a lesion. Thisstep can be used to determine whether or not a first ablating stepproduced sufficient removal or alteration of the electrical conductionof the tissue in order to block electrical conduction. If it isdetermined that sufficient ablation has not been achieved, thecontacting and ablating steps can be repeated until sufficientconduction block is confirmed. Intraoperative testing for conductionblock can include sensing for electrical signals on either side of anablation line, for example, to verify that the ablation line is complete(e.g., transmural) and continuous, and that electrical impulses are notcrossing the ablation line. Testing for conduction block can alsoinclude sensing for electrical signals on the ablation line that hasbeen created. In some embodiments, a sensing pen, such as a bipolarradiofrequency pen, can be placed on the ablation line itself, and thestrength of the sensed electrical signals can be determined. Forexample, it may be determined that a sensor placed on an ablation linemay demonstrate a reduction in amplitude of the EKG, such as an 80%, or90% reduction in amplitude of the EKG, which can be an indication of thedegree of ablation. Intraoperative electrophysiologic testing can beperformed, for example, by measuring the change in conductive propertiesof the tissue as it is being ablated. In some embodiments,intraoperative testing for can include testing for uni- orbi-directional block. The presence of uni- or bi-directional block canbe confirmed with a sensing device, such as the combination ablation andsensing device disclosed above. For example, cardiac tissue can betested for “entrance” block, meaning that an electrical signal orimpulse cannot pass from the atrial side of a lesion to the pulmonaryveins. If a subject is in sinus rhythm, the tissue can also be testedfor “exit” block, meaning that an electrical signal or impulse cannotpass from the pulmonary veins to the atrial tissue on the other side ofan ablation line. If both “entrance” and “exit” block is present, thenbidirectional block can be confirmed. If the subject is not in sinusrhythm (e.g., atrial fibrillation), only unidirectional “entrance” blockcan be confirmed, as it is not possible to evaluate whether or not anelectrical signal has traveled from the pulmonary veins to the atrialtissue in the presence of atrial fibrillation.

After the ganglionic plexi have been mapped and ablated, a soft tissuedissector can then be re-introduced through the anterior, or cephaladport incision (element 120 in FIG. 1) with a flexible guiding element,such as the Glidepath™ Transfer Tape (Atricure, Inc., Cincinnati, Ohio),or a red rubber catheter, such as a 14 French catheter, or similardevice, attached. The flexible guiding catheter or tape can then beplaced through the transverse sinus 202 with the tip posterior to theright set of pulmonary veins. The dissector with the attached guidingcatheter or tape can be maneuvered until the tip exits through theoblique sinus 201 between the right inferior pulmonary vein and the IVC.The guiding catheter or tape can be grasped and pulled outside of thechest, and the dissector disarticulated and removed. The guidingcatheter or tape now forms a path between the transverse sinus and theoblique sinus, shown as element 270 in FIG. 2. Alternatively, theguiding catheter can be placed from the oblique sinus to the transversesinus. The distal end of the Glidepath catheter can be attached to anablation device, such as an Isolator® Synergy™ Cardiac Ablation Clamp(Atricure, Inc., Cincinnati, Ohio) or other similar device, as disclosedabove.

Once the distal end of the Glidepath catheter is attached to an ablationdevice, the ablation device can be introduced into the right hemithoraxand the guiding catheter tape is used to guide one jaw of the clampbehind the right pulmonary veins while the other jaw is passed in frontof the veins, as shown in the front view of the heart as in FIG. 3. Inthis view, the left atrium is indicated as LA, the right atrium isindicated by RA, the left ventricle by LV, and the right ventricle byRV. Clamping of the left pulmonary veins is shown for illustration inFIG. 3. Clamping of the right pulmonary veins, although not shown, canbe performed in a similar manner. In some embodiments, while clampingthe right pulmonary veins, some or all of the inter-atrial groovetissue, where ganglionic plexi can be located, can be included in tissueto be ablated.

The ablation clamp 310 is shown, in this embodiment, as having one jawin front (element 325) of the left superior pulmonary vein 315 and theleft inferior pulmonary vein 320, and one jaw behind the veins (element330). The process of ablating the atrial tissue surrounding thepulmonary veins ablation can be continued until sufficient conductionblock is achieved, such as with 1 to 4 applications of the clamp, suchas two applications or more, or three applications or more, etc.Bidirectional block (e.g., an electrical signal is not transmitted fromeither direction) can then be confirmed with a sensing device, such asthe combination ablation and sensing device disclosed above. In someembodiments, each pulmonary vein can be tested individually forbidirectional block for both pacing and sensing. After bidirectionalblock is confirmed, the ablation device, such as a clamp, and theguiding catheter or tape can be removed. This completes the ablation, orelectrical isolation of tissue around the right set of pulmonary veins,which is shown as element 410 in FIG. 4.

Additional epicardial ablation lines can be made in order to blockaberrant conduction through other areas of the heart. A first epicardialablation line connecting the right inferior pulmonary vein to the leftinferior pulmonary vein through the oblique sinus can be made withmultiple stamping ablation applications of an ablation device such asthe bipolar radiofrequency pen described above. The process of ablationcan be continued until sufficient conduction block along the linebetween the right inferior pulmonary vein and the left inferiorpulmonary vein is achieved, such as with 1 to 4 applications of theclamp, such as two applications or more, or three applications or more,etc.

FIG. 4 provides a schematic view of the heart from the posterior aspect,illustrating a map of the ablation lesions created using the methods ofthe subject invention. The ablation line described above which connectsthe right inferior pulmonary vein to the left inferior pulmonary vein isshown as element 440 in FIG. 4. Anatomic landmarks include the inferiorvena cava (IVC) 401, superior vena cava (SVC) 402, right atrialappendage 403, right atrium 404, right superior pulmonary vein 405,right inferior pulmonary vein 406, left inferior pulmonary vein 407,left superior pulmonary vein 408, left ventricle 409, coronary sinus411, aorta 412, and left atrial appendage 413.

Although the most common pulmonary vein anatomy is shown in FIG. 2, withtwo right pulmonary veins 204 and two left pulmonary veins 203, themethods of the subject invention can also be used in patients withanatomic variants. For example, in most patients, the right pulmonaryveins include a right superior pulmonary vein and a right inferiorpulmonary vein as shown in FIG. 2, however in some patients the rightpulmonary veins can also include anatomic variants such as a commontrunk of the right pulmonary veins, or a supernumerary vein such as aseparate right middle pulmonary vein which drains the right middle lobeof the lung.

In addition to a line connecting the right inferior pulmonary vein tothe left inferior pulmonary vein, a second connecting ablation line canbe made from the right superior pulmonary vein to left superiorpulmonary vein through the transverse sinus posterior to the aorta andthe main pulmonary artery in the same manner. An ablation lineconnecting the right superior pulmonary vein to the left superiorpulmonary vein is shown as element 430 in FIG. 4.

A third connecting ablation line which can be produced with the subjectmethods extends from the superior pulmonary vein connecting ablationline across the dome of the left atrium to the fibrous trigone. Thefibrous trigone is an area at the aorto-mitral confluence, at the baseof the left coronary and non-coronary commissure of the aortic valve.Exposure to allow creation of this ablation line can be facilitated byusing an instrument inserted through the superior port, e.g., a port inthe 2^(nd) ICS, or 3^(rd) ICS, including the 3^(rd) ICS medial to theanterior axillary line, which is suitable for retracting tissue (e.g., asoft tissue dissector) which can retract the aorta medially, and theright atrial appendage laterally. A lesion located along this line canbe important for preventing atypical atrial flutter and left atrialtachycardia. This third ablation line (shown as element 450 in FIG. 4)forms an interconnecting or T-configuration ablation line with thesecond ablation line connecting the superior right and left pulmonaryveins (element 430).

An additional ablation line can be made from the lesion connecting theright and left inferior pulmonary veins 440 to the coronary sinus, shownas element 480 in FIG. 4. Creation of this ablation line can befacilitated by using an instrument inserted through the most cephaladport (e.g., a port in the 2nd intercostal space, or in the 3rdintercostal space medial to the anterior axillary line) for retractionof the heart anteriorly and retraction of the pericardium laterally.Collateral damage to the circumflex coronary artery can be avoided bydirect visualization with the thoracoscope, as well as by creating anablation line that intersects the coronary sinus sufficiently distal tothe coronary sinus ostium, or opening, such that it decreases the riskof damage to the circumflex artery. Verification that the cardiac tissuedown to the level of the mitral valve annulus has been reached can beevaluated by transesophageal echocardiography as well as by sensing ofatrial and ventricular electrograms, such as with a sensing bipolar pen.

Additional lesions which can be produced from the right thoracoscopicapproach include a vertically-oriented ablation line connecting thesuperior vena cava (SVC) to the inferior vena cava (IVC), which can bemade in the same manner as disclosed above, shown as element 500 in FIG.4. Furthermore, a T-ablation line can be formed which connects thevertical line connecting the SVC to the IVC (element 500) with thelateral aspect of the encircling right pulmonary vein isolation ablationline (element 410), thereby creating a continuous line across thelateral aspect of the atrial septum. This lesion is shown as element 490in FIG. 4.

In some instances, the methods of the subject invention further includefocal ablation of one or more complex fractionated atrial electrograms(CFAEs). CFAEs are areas of cardiac atrial tissue with characteristicmorphologically distinct electrograms that may contribute to theinitiation and/or propagation of arrhythmias. CFAEs can be located byinterrogation from the epicardial surface with a sensing device, such asa sensing pen. One or more complex fractionated atrial electrograms canbe ablated from the epicardial approach, using the devices as disclosedabove. CFAEs can be sensed and ablated in both left and right atria, aswell as in both the superior and inferior vena cavae. The methods caninclude performing the ablating steps one or more times until it isdetermined that the CFAE has been ablated (e.g. the characteristicmorphology of a complex fractionated atrial electrogram is no longerdetected in the region that has been ablated). Further details oftechniques of mapping and ablation of CFAEs that can be adapted for usewith the subject methods are disclosed in the publication by Nademanee,et al., entitled “A new approach for catheter ablation of atrialfibrillation: mapping of the electrophysiologic substrate”. Followingthe completion of the ablation procedure, a chest tube can be insertedfor venting and the right lung re-inflated.

For a left thoracoscopic approach, the operating table can be tiltedslightly to the right side with a slight tilt, such as a 15 degree tilt.After the left lung is deflated, one or more openings can be created inthe left side of the chest. In one embodiment, four ports can beutilized for performing the methods of the subject invention, as shownin FIG. 1. The first port, shown as element 115 in FIG. 1, can be placedin the 3^(rd) or 4^(th) intercostal space (ICS) 1 centimeter posteriorto the anterior axillary line. A thoracoscope can be introduced and theleft hemithorax visually inspected. Humidified CO₂ can be introducedinto the thoracic cavity at a pressure sufficient to allow adequatevisualization for the methods of the invention (e.g., 8 mm Hg pressure).A second port can be placed in the 2^(nd) ICS 1 to 2 cm medial toanterior axillary line, shown as element 125 in FIG. 1. The placement ofthis most cephalad port on the left allows for the exposure forcompletion of the superior connecting ablation line in the roof of theleft atrium. The most cephalad port (e.g., a port in the 2^(nd) ICS) canalso utilized in the creation or completion of the ablation line fromthe superior pulmonary vein connecting ablation line across the dome ofthe left atrium to the fibrous trigone (element 450). A third port canbe placed in the 5^(th) ICS mid axillary line, shown as element 135 inFIG. 1. The fourth port, element 145 in FIG. 1, can be placed in the6^(th) ICS in the anterior axillary line.

A second thoracoscopic grasping forceps can be introduced through themost caudal port. A second opening can be created in the pericardium onthe left side to allow access to the epicardial surface of the heart. Insome embodiments, the pericardium can be opened in the most dependentportion posterior to the left phrenic nerve and the opening can be thenextended to the level of the diaphragm. The pericardial opening can beenlarged posterior and parallel to the phrenic nerve extending cephaladand superior to the right pulmonary artery. An endograsper orendoKittner can then be introduced through the third port. One or moretraction sutures can be placed on the edges of the pericardium, toexpose the left atrial appendage in its entirety. As disclosed above, insome embodiments, this is facilitated utilizing an Endo Stitch™(Autosuture™, Covidien, Mansfield, Mass.), or other similar suturedevice.

A combination ablation and sensing device as described above can beintroduced into the thoracic cavity via the third port. The sensingportion of the device can be used for sense pulmonary vein potentials,to create a baseline map of the left pulmonary vein potentials.Additionally, in some embodiments, autonomic ganglionic plexi can bemapped with high-frequency stimulation and then focally ablated, asdisclosed above for the right side.

In some embodiments, the ligament of Marshall and posterior pericardialattachments can be divided, or separated, from the pulmonary artery downto the dome of the left atrium, and then ablated. The ligament ofMarshall is a vestigial structure of the vein of Marshall which can alsobe a source of arrhythmia. Exposure to allow ablation of the ligament ofMarshall can be facilitated by using an instrument inserted through thesuperior port, e.g., a port in the 2^(nd) ICS, or 3^(rd) ICS, includingthe 3^(rd) ICS medial to the anterior axillary line, which is suitablefor retracting tissue (e.g., an endoscopic fan retractor, or a softtissue dissector such as an endoscopic Kittner) which can retract theleft atrial appendage medially and caudally. Simultaneous retraction ofthe left pulmonary artery cephalad, or in a superior direction, canallow access to the ligament of Marshall. After the ligament of Marshallis divided and ablated, a dissector, such as the Wolf dissector, can bethen introduced through the 5^(th) ICS port incision (element 135 inFIG. 1) with a guiding element, such as the Glidepath™ Transfer Tape ora red rubber catheter attached. The dissector can be placed into theoblique sinus, and maneuved until the tip passes through the transversesinus superior and medial to the left superior pulmonary vein.Alternatively, the guiding catheter can be placed from the transversesinus to the oblique sinus. The Glidepath catheter is grasped and pulledout of the chest, and the dissector disarticulated and removed. Theguiding catheter or tape now forms a path between the transverse sinusand the oblique sinus, shown as element 280 in FIG. 2. The distal end ofthe Glidepath catheter, which has been attached to an ablation device,can then be introduced into the left hemithorax. The guiding element,such as a catheter, can be used to guide one jaw 330 of the clamp 310 inFIG. 2 behind the left pulmonary veins while the other jaw 325 is passedin front of the veins. The process of ablating the atrial tissuesurrounding the pulmonary veins ablation can be continued untilsufficient conduction block is achieved, such as with 1 to 4applications of the clamp, including two applications or more, or threeapplications or more, etc.

In some embodiments, after ablation has been performed, the cardiactissue can be tested intraoperatively for sufficient conduction block.In some embodiments, each pulmonary vein is tested individually forbidirectional block for both pacing and sensing. After sufficientconduction block is confirmed, the ablation device and the guidingelement can be removed. This completes the ablation, or electricalisolation of tissue around the left set of pulmonary veins, which isshown as element 420 in FIG. 4.

The heart can then be retracted anteriorly in order to complete theinferior epicardial ablation line 440 in FIG. 4 by connecting this lineto the left pulmonary vein encircling ablation line 420 using acombination ablation and sensing device. The superior epicardialablation line 430 can be completed by connecting to the left pulmonaryvein encircling ablation line 420. An additional ablation line (element460) can then be made from the base of the left atrial appendage whichcan be connected to the left pulmonary vein encircling ablation line420.

In some embodiments, the methods of the subject invention furtherinclude amputation of the left atrial appendage (element 470). The leftatrial appendage can be a frequent source of thromboemboli in patientswith atrial fibrillation. The left atrial appendage can be occludedutilizing an endoscopic no-knife stapling device, such as an Ethicon™ EZ45 NK device (Ethicon Endo-Surgery, Inc., Cincinnati, Ohio) or a leftatrial appendage clip (LAA) clip (AtriCure Inc., Westchester, Ohio)which is placed at the base of the appendage. The line of exclusion forthe left atrium is shown as element 470 in FIG. 4. Placement can beconfirmed by tranesophageal echocardiography. In embodiments in whichstaples are used, an initial row of staples can be placed across thebase of the left atrial appendage, and if it is determined that theexclusion is incomplete, one or more additional rows of staples can beplaced. After the exclusion is complete, the left atrial appendage canbe amputated with a cutting stapling device, such as an Ethicon EZ 45 Kdevice, and the appendage removed.

Elements of the Cox maze III set of lesions that can be produced withthe methods of the subject invention therefore can include a rightpulmonary vein encircling ablation line 410 as shown in FIG. 4, a leftpulmonary vein encircling ablation line 420, a superior connectingablation line connecting the right and left pulmonary vein encirclinglines 430, and an inferior connecting ablation line connecting the rightand left pulmonary vein encircling lines 440. The combination ofablation lines 410, 420, 430, and 440 comprises what is known as the“box lesion” set. In addition, an ablation line connecting the superiorablation line to the fibrous trigone 450, an ablation line connectingthe superior ablation line to the left atrial appendage 460, a leftatrial appendectomy 470, and an ablation line extending from theinferior connecting ablation line to the coronary sinus 480 canadditionally be produced. In some embodiments, the set of lesions caninclude an ablation line in the posterior wall of the right atriumconnecting the superior vena cava to the inferior vena cava 500, and anablation line connecting the right pulmonary vein encircling line to anablation line in the posterior wall of the right atrium connecting thesuperior vena cava to the inferior vena cava 490. In addition, in someinstances the methods can include ablation of autonomic ganglionicplexi. In some embodiments, the methods also include ablation of complexfractionated atrial electrograms, as discussed above.

Although the above ablation lines or lesions have been described in aparticular order, the methods of the invention can also include creationof the lesions in any suitable order. For example, the superiorepicardial ablation line 430 in FIG. 4 can be completed by connecting tothe left pulmonary vein encircling ablation line 420, and then theinferior epicardial ablation line 440 can be completed by connectingthis line to the left pulmonary vein encircling ablation line 420.

Furthermore, although the methods of producing ablation lines disclosedabove have been described as being performed sequentially, such that theablation lines are produced first on one side followed by the otherside, in some embodiments the methods of the invention can also includethe production of ablation lines from both sides simultaneously. Themethods of the subject invention can also include the simultaneous useof thoracoscopic instruments from both sides, such as for example, if athoracoscopic instrument inserted from the left is used to produce anablation line, and a thoracoscopic instrument inserted from the right isused for retraction, for illumination, etc.

After completion of the ablation procedure as outlined above, the set oflesions that have been created can be tested by attempting to induce anarrhythmia, e.g., atrial fibrillation, by atrial burst pacing. Forexample, the cardiac tissue can be stimulated at 20 mA for 5 seconds. Ifan attempt to induce an arrhythmia results in sustained AF, for example,then this can indicate that atrial tissue with the potential ofgenerating or maintaining AF persists. Sustained atrial fibrillation canbe defined as AF lasting ≧10 minutes. If an arrhythmia can be induced atthe conclusion of the procedure, then additional ablation can beperformed. This can include additional ablation, for example, inpositive GP sites, or additional ablation in one of the connectingablation lines, e.g., the connecting ablation line to the left atrialappendage, or ablation of a complex fractionated atrial electrogram,etc.

By this method, an atrial arrhythmia, such as atrial fibrillation, canbe successfully treated using a completely thoracoscopic method toproduce a set of lesions chosen from among a group of Cox maze III setof lesions as disclosed above. Using the methods of the subjectinvention, an epicardial Cox maze III ablation procedure can besuccessfully completed on a beating heart, without the need to place thepatient on cardiopulmonary bypass. In addition, the methods can includethoracoscopically producing a lesion in the ganglionic plexi. Successfulablation can be verified with intraoperative electrophysiologic testing.

The subject methods find use in treating a cardiac arrhythmia, such asatrial fibrillation, by the epicardial ablation of cardiac tissuethrough openings in a subject's body using thoracoscopic methods.Although the Cox maze III set of lesions can be used for the treatmentof AF, the methods of the subject invention can also be used to treatmultiple cardiac arrhythmias, including but not limited to: all types ofatrial fibrillation, including paroxysmal, persistent, long-standingpersistent, and permanent AF, atrial flutter; atrioventricular (AV) nodereentrant tachycardias; and atrioventricular (AV) reentry tachycardia(such as Wolff-Parkinson-White syndrome), and therefore any appropriatecardiac arrhythmia may be treated as described herein. Furthermore, themethods of the subject invention may also be used in combination withother thoracoscopic procedures. Although the methods as described aboveare directed to creation of a Cox maze III set of lesions in the atria,the methods of thoracoscopically producing a set of lesions can also beused to treat ventricular arrhythmias.

The subject methods also include the step of diagnosing a patient inneed of surgical treatment for a cardiac arrhythmia, e.g., atrialfibrillation. Patients who need surgical treatment for an arrhythmia caninclude, for example, patients who cannot be anticoagulated, or patientswho have failed medical therapy, or who cannot tolerate the side effectsof anti-arrhythmic drugs.

Cardiac arrhythmias can have many different causes. For example, atrialfibrillation can have both cardiovascular causes (such as hypertensiveheart disease, coronary artery disease, valvular heart disease,cardiomyopathies) and non-cardiovascular causes (such as lung disease,obesity, sleep apnea, metabolic disorders, toxins).

Therefore, the signs and symptoms associated with a cardiac arrhythmiawill vary depending on the arrhythmia, and upon any associatedcondition. Signs and symptoms can include abnormal awareness of theheartbeat, or palpitations, lightheadedness or dizziness, shortness ofbreath, decreased exercise tolerance, fatigue, fainting. Somearrhythmias can result in cardiac failure, cardiac arrest, or suddendeath. Some forms of arrhythmia may not cause symptoms, but can increasethe risk of stroke. For example, patients with atrial fibrillation havean increased risk of embolism, transient ischemic attacks (TIAs), andstroke. Cardiac arrhythmias are often first detected by an abnormalperipheral pulse, or by auscultation of the heart with a stethoscope.These methods may not be sufficient to diagnose specific arrhythmias,but can give a general indication of the heart rate and whether it isregular or irregular.

Diagnostic tests can include physical examination, electrocardiogram(EKG; ECG); a Holter monitor, which is an EKG recorded over a 24-hourperiod to detect arrhythmias that may happen briefly and unpredictablythroughout the day, imaging studies such as chest x-ray, ultrasound,computerized tomography (CT), magnetic resonance imaging (MRI), nuclearmedicine studies such as a nuclear myocardial stress test, for example.Additionally, invasive studies including cardiac catheterization withelectrophysiologic studies may be performed.

Treatment for arrhythmias, including AF, can include anti-arrhythmicdrugs to prevent or control arrhythmias, and maintain the normal sinusrhythm of the heart. Medication to prevent clotting is also indicated inpatients who are at risk for clots and emboli, which are clots whichtravel elsewhere in the body and can cause strokes, for example.Invasive treatments can include catheter ablation or modification of theatrioventricular (AV) node, with concomitant pacing of the heart, andcatheter or surgical ablation procedures, such as the Cox maze IIIprocedure.

The description of the present invention is provided herein in certaininstances with reference to a subject or patient. As used herein, theterms “subject” and “patient” refer to a living entity such as ananimal. In certain embodiments, the animals are “mammals” or“mammalian,” where these terms are used broadly to describe organismswhich are within the class mammalia, including the orders carnivore(e.g., dogs and cats), rodentia (e.g., mice, guinea pigs, and rats),lagomorpha (e.g., rabbits) and primates (e.g., humans, chimpanzees, andmonkeys). In certain embodiments, the subjects, e.g., patients, arehumans.

The following example is offered by way of illustration and not by wayof limitation.

Experimental

A patient with a diagnosis of atrial fibrillation was prepared for athoracoscopic epicardial ablation procedure in a conventional manner.The patient was placed supine on the operating table with both arms athis side and slightly flexed at the elbows. A roll was placedtransversely across and underneath the tips of the scapulae. Generalanesthesia was administered with a double-lumen endotracheal tube forsingle lung ventilation. A right internal jugular venous introducersheath was inserted for central venous pressure monitoring as well asfor intravenous fluid administration. Transesophageal echocardiographymonitoring was performed during the entire procedure.

Right Thoracoscopic Approach

The table was tilted slightly to the left side with a 15 degree tilt.The right lung was deflated. Four ports were utilized. The first 12 mmport was placed in the 4^(th) intercostal space (ICS) 1 centimeterposterior to the anterior axillary line. The thoracoscope was thenintroduced and the right hemithorax visually inspected. Humidified CO₂insufflation (8 mm Hg pressure) was instituted and maintained throughoutthe procedure. The second 12 mm port was placed in the 3^(rd) ICS 1 cmmedial to anterior axillary line. A 5 mm port was placed in the 5^(th)ICS mid-axillary line. The third 12 mm port was placed in the 6^(th) ICSin the anterior axillary line, for a total of four ports. Thepericardium was opened cephalad to the confluence of the right atrialappendage and ascending aorta. The opening was extended cephalad, orsuperiorly, to the level of the aorta, 2 cm anterior and parallel to theright phrenic nerve, and was extended inferiorly to the level of theinferior vena cava (IVC). Two traction sutures were placed andexteriorized. This was facilitated utilizing an Endo Stitch™×2(Autosuture™, Covidien, Mansfield, Mass.). The oblique sinus was openedbluntly with endoKittner. The transverse sinus was entered withretraction of the SVC anteriorly with endoKittner and entry into thetransverse sinus was confirmed with visualization of the left atrialappendage. The Wolf™ Lumitip™ dissector (Atricure, Inc., Cincinnati,Ohio) was introduced through the oblique sinus and then articulated withthe tip exiting in the transverse sinus posterior to the right set ofpulmonary veins. The posterior space between the pericardium and leftatrium was then enlarged with blunt dissection. The dissector was thenremoved.

Atrial electrograms and pulmonary vein potentials were then sensed torecord a baseline. Autonomic ganglionic plexi were mapped withhigh-frequency stimulation and then active GPs, defined as thoseresulting in a lengthening of the R-R interval of greater than 50%, werefocally ablated. The Lumitip dissector was then introduced through theanterior/cephalad port incision (port site #2) with the Glidepath™Transfer Tape (Atricure, Inc., Cincinnati, Ohio) catheter attached. Thiswas placed through the transverse sinus with the tip posterior to theright set of pulmonary veins. The dissector was then articulated withthe tip exiting through the oblique sinus between the right inferiorpulmonary vein and IVC. The Glidepath catheter was grasped andexteriorized and the dissector disarticulated and removed. The distalend of the Glidepath catheter was attached to the bipolar radiofrequency(RF) Isolator® Synergy™ Cardiac Ablation Clamp (Atricure, Inc.,Cincinnati, Ohio) and then was introduced into the right hemithorax andthe catheter was used to guide the lower jaw of the clamp behind theright pulmonary veins while the upper jaw was passed in front of theveins. Five applications of the clamp were sufficient to provideconduction block. The patient was defibrillated into sinus rhythm andbidirectional block was confirmed with the bipolarpace/sense/stimulation pen. After bidirectional block was confirmed, theclamp and catheter were removed.

Epicardial ablation lines were then made connecting the right inferiorpulmonary vein to the left inferior pulmonary vein through the obliquesinus with multiple stamping ablation applications of the bipolarablation pen. A second connecting ablation line was made from rightsuperior pulmonary vein to left superior pulmonary vein through thetransverse sinus posterior to the aorta and main pulmonary artery in thesame manner. Then a connecting ablation line from the fibrous trigoneunder the aorta was made as an interconnecting or T-ablation line to thesuperior vein connecting ablation line. An ablation line connecting thesuperior vena cava to the inferior vena cava was then made and finally aT-ablation line from this line to the encircling right pulmonary veinisolation ablation line was made, thereby ablating the lateral aspect ofthe atrial septum. Complex fractionated atrial electrograms were mappedand focally ablated at the base of the right atrial appendage as well asthe lateral free wall of the right atrium. A 24 Fr chest tube wasinserted for venting and the right lung inflated.

Left Thoracoscopic Approach

The table was tilted toward the right 15 degrees and the left lung wasdeflated. Four ports were utilized. The first 12 mm port was placed inthe 4^(th) intercostal space (ICS) 1 centimeter posterior to theanterior axillary line. The endoscope was then introduced and the lefthemithorax visually inspected. Humidified CO₂ insufflation (8 mm Hgpressure) was instituted and maintained throughout the procedure. Thesecond 12 mm port was placed in the 2^(nd) ICS 2 cm medial to anterioraxillary line. A third 5 mm port was placed in the 6^(th) ICS midaxillary line. The third 12 mm port was placed 1 cm posterior to themid-axillary line in the 5^(th) ICS. The pericardium was opened in themost dependent portion posterior to the left phrenic nerve and extendedto the level of the diaphragm. The opening was then enlarged posteriorand parallel to the phrenic nerve extending cephalad and superior to theright pulmonary artery. A traction suture was placed anteriorly toexpose the left atrial appendage in its entirety and exteriorizedthrough a stab incision in the 2nd ICS in the mid-clavicular line.

With the patient in sinus rhythm, pulmonary vein potentials were thensensed as well as paced. Autonomic ganglionic plexi were mapped withhigh-frequency stimulation and then focally ablated. The ligament ofMarshall and posterior pericardial attachments were divided from thedome of the left atrium. The Lumitip dissector was then introducedthrough the 5^(th) ICS port incision with the Glidepath catheterattached. The dissector was then articulated with the tip exitingsuperior and medial to the left superior pulmonary vein. The Glidepathcatheter was grasped and exteriorized and the dissector disarticulatedand removed. The distal end of the Glidepath catheter was alreadyattached to the bipolar radiofrequency (RF) Isolator® Synergy™ CardiacAblation Clamp (Atricure, Inc., Cincinnati, Ohio) which was thenintroduced into the left hemithorax. The catheter was used to guide thelower jaw of the clamp behind the left pulmonary veins while the upperjaw was passed in front of the veins. Six applications of the clamp weresufficient to provide conduction block. Bidirectional block was thenconfirmed with the bipolar pace/sense/stimulation pen. Afterbidirectional block was confirmed, the clamp and catheter were removed.

The heart was then retracted anteriorly and then the inferior epicardialablation line was completed by connecting to the left pulmonary veinencircling ablation line. The superior epicardial ablation line wascompleted by connecting to the left pulmonary vein encircling ablationline. An ablation line was then made from the mid portion of the leftatrial appendage down to its base and then connected to the leftpulmonary vein encircling ablation line. A connecting ablation line tothe coronary sinus from the inferior connecting ablation line was thenperformed. The Cox maze III lesion set was then completed.

Amputation of the Left Atrial Appendage

The left atrial appendage was occluded utilizing an endoscopic no-knifestapling device (Ethicon EZ 45 NK) which was placed at the base of theappendage and confirmed by tranesophageal echocardiography. This allowedfor safe occlusion. Finally, the left atrial appendage was amputatedwith a cutting stapling device (Ethicon EZ 45 K). The appendage was thenremoved.

Confirmation of Non-Inducibility

Non-inducibility of AF was assessed by atrial burst pacing at a 200 mseccycle length for 5 seconds. Sustained AF was defined as AF lasting >/=30seconds.

At the conclusion of the procedure, the subject was in normal sinusrhythm. The chest and skin incisions were then closed to complete theprocedure. The procedure took 3 hours and 20 minutes to complete.Follow-up evaluation of the patient by 21 day mobile cardiac outpatienttelemetry at 6 months and 1 year demonstrated documented maintenance ofsinus rhythm without anti-arrhythmic medication.

All publications and patent applications cited in this specification areherein incorporated by reference as if each individual publication orpatent application were specifically and individually indicated to beincorporated by reference. The citation of any publication is for itsdisclosure prior to the filing date and should not be construed as anadmission that the present invention is not entitled to antedate suchpublication by virtue of prior invention.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, it is readily apparent to those of ordinary skill in theart in light of the teachings of this invention that certain changes andmodifications may be made thereto without departing from the spirit orscope of the appended claims.

What is claimed is:
 1. A method of treating a subject for cardiacarrhythmia, the method comprising thoracoscopically producing a Cox mazeIII set of lesions in a manner sufficient to treat the subject for thecardiac arrhythmia, wherein the Cox maze III set of lesions comprises aright pulmonary vein encircling ablation line, a left pulmonary veinencircling ablation line, a superior connecting ablation line connectingthe right and left pulmonary vein encircling lines, and an inferiorconnecting ablation line connecting the right and left pulmonary veinencircling lines.
 2. The method according to claim 1, whereinthoracoscopically producing comprises making a thoracoscopic bodyopening that measures no more than 12 millimeters in greatest dimension.3. The method according to claim 2, wherein the method comprisesintraoperative testing to confirm the presence of a lesion.
 4. Themethod according to claim 1, wherein at least one lesion comprises atransmural lesion.
 5. The method according to claim 1, wherein themethod further comprises thoracoscopically producing a lesion in aganglionic plexus.
 6. The method according to claim 2, whereinthoracoscopically producing comprises making bilateral thoracoscopicbody openings.
 7. The method according to claim 6, wherein the bilateralthoracoscopic body openings comprise four thoracoscopic body openings oneach side.
 8. The method according to claim 2, wherein the thoracoscopicbody opening is an opening in a second intercostal space.
 9. The methodaccording to claim 2, wherein the thoracoscopic body opening is anopening in a third intercostal space medial to the anterior axillaryline.
 10. The method according to claim 1, wherein the Cox maze III setof lesions further comprises an ablation line connecting the superiorconnecting ablation line to the base of the left atrial appendage. 11.The method according to claim 1, wherein the Cox maze III set of lesionsfurther comprises a left atrial appendectomy.
 12. The method accordingto claim 1, wherein the Cox maze III set of lesions further comprises anablation line connecting the superior connecting ablation line to thefibrous trigone.
 13. The method according to claim 1, wherein the Coxmaze III set of lesions further comprises an ablation line extendingfrom the inferior connecting ablation line to the coronary sinus. 14.The method according to claim 1, wherein the Cox maze III set of lesionsfurther comprises an ablation line in the posterolateral wall of theright atrium connecting the superior vena cava to the inferior venacava.
 15. The method according to claim 1, wherein the Cox maze III setof lesions further comprises an ablation line from the right pulmonaryvein encircling ablation line to the posterolateral wall of the rightatrium.
 16. The method according to claim 1, wherein the Cox maze IIIset of lesions further comprises focal ablation of a complexfractionated atrial electrogram.
 17. The method according to claim 1,wherein thoracoscopically producing comprises contacting cardiac tissuewith an ablation device.
 18. The method according to claim 17, whereinthe ablation device is a clamping device.
 19. The method according toclaim 17, wherein the ablation device is an elongated cylindricaldevice.
 20. The method according to claim 17, wherein the ablationdevice is a bipolar radiofrequency device.
 21. The method according toclaim 17, wherein the ablation device is a laser energy device.
 22. Themethod according to claim 17, wherein the ablation device is a microwaveenergy device.
 23. The method according to claim 17, wherein theablation device is a thermal energy device.
 24. The method according toclaim 17, wherein the ablation device is an ultrasound device.
 25. Themethod according to claim 17, wherein the ablation device is acryoablation device.
 26. The method according to claim 1, wherein thecardiac arrhythmia comprises atrial fibrillation.